AIDS Therapy in Africa

Elizabeth Johnston
School of Medicine
Stanford University
December 2001

I am studying the effects of drug treatment on HIV-infected people in Zimbabwe as part of a collaboration of Stanford and Zimbabwean researchers. There are two parts to this study. First, we are examining HIV in pregnant women who have been provided treatment to reduce transmission of the virus to their infants. Second, we are characterizing viruses from twenty-eight men and women who have been treated with anti-HIV drugs for the past year but have not been closely monitored. By studying these two groups, we hope to identify problems associated with taking anti-HIV drugs in countries where health care is limited.

For many people living in third world countries, medical intervention for HIV is not possible due to the high costs of therapy. In Zimbabwe, a country in southern Africa, more than 1.5 million people carry the HIV virus. The death rate in this part of the world has gone up dramatically over the past two decades due to HIV. In contrast, the death rate for people with HIV in the US and Western Europe has declined over the past ten years because of the availability of drugs that keep the virus in check.

Anti-HIV drugs can also reduce transmission of HIV from a pregnant woman to her child. About 25 to 40% of women pass the virus to their child, either in utero or during birth. However, this rate can be decreased by 50% when the woman is given an antiretroviral drug called nevaripine at the onset of labor and her baby is given a dose of the same drug at birth. We are studying whether this single dose of drug given to the mother leads to changes in the virus that cause the virus to be resistant to the drug and how soon these viral changes might disappear. This is important to understand since many of these women will become pregnant again and we want to determine if this therapy might still be effective for a subsequent pregnancy. So far we have found virus changes that cause nevaripine-resistant virus in 28% of patients. This rate is similar to what other studies have found. We will also be looking at the prevalence of these changes in virus found in breastmilk since mothers can also pass the virus to their baby after birth through nursing.

Currently, while most drugs given to HIV-infected individuals in countries like Zimbabwe involve prevention of mother to child transmission, a small number of people are able to afford anti-HIV drug regimens like those used in the US. A place called The Centre in Harare has been providing antiretroviral drugs to patients at low cost though the drugs are not always available and they are not always taken in the best way. We obtained blood samples from some patients to determine how well they are doing on therapy and to characterize the viruses that they carry. Some patients had low concentrations of HIV virus in their blood, indicating that their drug therapy is working. In contrast, many patients had higher concentrations of virus as well as low numbers of immune cells, indicating that their drug regimen is not effective and possibly should be changed to a different combination of drugs.

One characteristic of the viruses from The Centre patients is that these viruses are all subtype C HIV, the HIV virus that is prevalent in southern Africa. In contrast, most people with HIV in the US and Western Europe are infected with a slightly different HIV virus called subtype B. A distinguishing characteristic of subtype C virus has been that the vast majority of subtype C viruses use a protein called CCR5 to enter cells. In contrast, up to fifty percent of subtype B viruses utilize a different protein called CXCR4. Interestingly, fifty percent of the patients receiving anti-HIV drug treatment from The Centre had viruses that were subtype C and also used the protein CXCR4, while those patients not taking anti-HIV drugs only had viruses that used CCR5 to enter cells. We are currently characterizing these viruses to determine how they compare to other subtype B CXCR4-using viruses.

By studying the effects of HIV therapy on patients in a limited resource setting, we hope to identify possible problems that might arise from taking these drugs and determine if there are any problems that might be different compared to what has been observed in the US. In addition, we hope to investigate possible low cost therapies that would be possible to implement in countries like Zimbabwe.